Salt reduction in hypertension – does it make a difference?

From Kempner’s rice diet to studies based on unacculturated tribes, such as the Yanomamo civilisation to whom salt was unknown, the clinical effects of salt on blood pressure have been recognised as far back as the 1940s.[1] Sodium, the culprit ingredient in salt, mediates hypertension through processes such as water retention, vascular remodelling and endothelial dysfunction.[2] 

For the Yanomami, hypertension was non-existent. A mean blood pressure of 96.0/60.6 mmHg was observed in these individuals, with further studies demonstrating a mean sodium excretion of 0.9 mmol/24 h.[3] (To provide some context, the normal reference approximately ranges from 40–220 mmol/24 h for those of us on contemporary, salt-inclusive diets.[4]) 24-hour urinary sodium excretion, regarded as the most accurate measure for assessing sodium intake, has been associated with an increased cardiovascular risk in a dose-dependent manner.[5] Interestingly, some cohort studies have demonstrated a paradoxical increase in mortality associated with very low sodium levels, due to proposed mechanisms such as the activation of the renin–angiotensin–aldosterone system, electrolyte disturbances, increased sympathetic activity and elevated catecholamine levels, though larger epidemiological studies have failed to verify this.[2]

Blood pressure response to dietary sodium intake can be variable across individuals, suggesting that salt reduction may only be suitable for a particular subset of patients, though a reliable diagnostic test to identify these “salt-sensitive” patients is currently lacking. Regardless, the pathophysiological links between high sodium intake and hypertension, as well as adverse cardiovascular events, are well-established,[6] and current European Society of Cardiology guidelines for the management of hypertension advocate limiting daily dietary sodium intake to 2 g (equivalent to 5 g of salt) in adults (class 1A recommendation), in line with World Health Organization guidance.[7] In a meta-analysis by He et al, a reduction of 1.75 g of sodium/day was associated with a 5.4 and 2.8 mmHg reduction in systolic and diastolic blood pressures, respectively, in hypertensive patients, with a more pronounced effect observed in those with higher blood pressures, meaning those with uncontrolled or resistant hypertension may stand to achieve more benefit.[8] For some, this could be the distinction that spares them from requiring an additional antihypertensive pill or, more importantly, a heart attack or stroke.

Despite the emphasis on salt restriction, the practicalities of adhering to such a regimen can be challenging. Thus, Hornstrup et al sought to evaluate the feasibility of self-performed dietary sodium restriction in patients with treatment-resistant hypertension (TRH; those treated with three or more anti-hypertensive agents, with at least one being a diuretic), a difficult-to-manage cohort of hypertensive patients with an even higher risk of adverse events.[9] The authors also assessed the impact of salt limitation on patients’ blood pressure and evaluated whether processes involving nitric oxide, body water content and the renal handling of sodium had an impact on nocturnal and 24-hour blood pressure. Finally, they looked at the potential for erythrocyte sodium sensitivity (ESS) measurements to predict salt sensitivity in this cohort. 

The study, comprising only 15 patients, used a crossover design where the participants spent the first two weeks on their usual diet and subsequent two weeks on a self-performed sodium-restricted diet supplemented with sodium-free bread by the study team. Medication adherence was ensured through pill counts, and participants were given detailed instructions on how to reduce sodium, including suggestions for every meal and written guidance on foods to avoid. 

In short, the findings demonstrated a significant reduction in nocturnal and 24-hour systolic blood pressure, which was accompanied by a reduction in 24-hour urinary sodium excretion in all but one person. However, neither this, nor the decrease in body water content, correlated with the decrease in blood pressure. 

In contrast, plasma nitric oxide levels did increase and correlate with the blood pressure readings, and the authors attributed the blood pressure lowering effect to increased nitric oxide synthesis. Though this is plausible, other dietary changes, such as fruit intake, which were encouraged during the study period, may have influenced this. Finally, ESS measurements showed poor predictive ability for sodium sensitivity. A digest of the study can be read here.

While findings from this Danish study strengthen the evidence supporting the blood pressure-lowering effects of salt restriction, the remaining results are hypothesis-generating at best, due to the significant limitations of the study, such as its small sample size and short study duration. 

The authors conclude that self-performed dietary sodium restriction is feasible in this cohort, albeit admitting that patients would need to bake their own salt-free bread. One also wonders how likely patients would be to adhere to a stringent dietary regimen in the long-term, especially if significantly different to their usual meals. The beneficial effect of reduced sodium intake has been seen to diminish with time, in part due to poor dietary persistence.[7]

Nonetheless, efforts should be made to address dietary salt restriction in all patients, improve awareness of everyday sources of high sodium that commonly lead to under-estimation of self-reported salt intake, promote long-term adherence and signify importance of this single measure as a means to mitigate risk of adverse cardiorenal and vascular events.

References

1. Ha SK (2014) Dietary salt intake and hypertension. Electrolyte Blood Press 12: 7–18
2. Grillo A, Salvi L, Coruzzi P et al (2019) Sodium intake and hypertension. Nutrients 11: 1970
3. Oliver WJ, Cohen EI, Neel JV (1975) Blood pressure, sodium intake, and sodium related hormones in the Yanomamo Indians, a “no-salt” culture. Circulation 52: 146–51
4. Pagana KD, Pagana TJ. Mosby’s Manual of Diagnostic and Laboratory Tests (6th edition). Mosby, Maryland Heights, MO, USA
5. Ma Y, He FJ, Sun Q et al (2022) 24-hour urinary sodium and potassium excretion and cardiovascular risk. N Engl J Med 386: 252–63
6. World Health Organization (2012) Sodium Intake for Adults and Children. WHO, Geneva, Switzerland. Available at: https://www.who.int/publications/i/item/9789241504836 (27.10.23)
7. Williams B, Mancia G, Spiering W et al (2018) 2018 ESC/ESH Guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Cardiology (ESC) and the European Society of Hypertension (ESH). J Hypertens 36: 1953–2041
8. He FJ, Li J, MacGregor GA (2013) Effect of longer-term modest salt reduction on blood pressure. Cochrane Database Syst Rev 2013: CD004937 
9. Hornstrup BG, Hoffmann-Petersen N, Lauridsen TG, Bech JN (2023) Dietary sodium restriction reduces blood pressure in patients with treatment resistant hypertension. BMC Nephrol 24: 274